Erianin induces cell apoptosis through ERK pathway in human nasopharyngeal carcinoma

Liu, Yen-Tze; Hsieh, Ming‐Ju; Lin, Jen-Tsun; Chen, Gene; Lin, Chia-Chieh; Lo, Yu‐Sheng; Chuang, Yi‐Ching; Hsi, Yi‐Ting; Chen, Mu‐Kuan; Chou, Ming-Chih

doi:10.1016/j.biopha.2018.12.081

Cited by 42 publications

(27 citation statements)

References 24 publications

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“…We found that erianin increased Bim and Bax levels whereas decreased Bcl-2 and Mcl-1 levels, which were associated with UPRs upstream and apoptosis signals downstream in LNCaP cells (Figure 2F). In support of this, previous studies also identify that erianin upregulates Bim and Bax expression whereas downregulates Bcl-2 and Mcl-1 levels, leading to the activation of the intrinsic apoptosis signaling in hepatocellular carcinoma cells, bladder cancer cells, nasopharyngeal cancer cells and osteosarcoma cells (13,14,16,17). In addition, the Bcl-2 family has multiple functional interactions with Akt (protein kinase B), an oncogene that is highly expressed in almost all cancers.…”

Section: Discussionmentioning

confidence: 55%

“…Erianin is a major bibenzyl compound extracted from Dendrobium. This phytochemical has little toxicity in immortalized normal human hepatocytes and nasopharyngeal normal primary cells (12,13), whereas it has shown potent anti-tumor effects at nanomolar concentrations. Erianin induces oxidative stress, leading to apoptosis via the intrinsic apoptosis pathway (14)(15)(16)(17)(18), blocks the cell cycle at the G2/M phase (12,14,17), and has been recently found to trigger ferroptosis, an iron-dependent programmed cell death (19).…”

Section: Introductionmentioning

confidence: 99%

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Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

et al. 2021

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Prostate cancer is the second most prevalent malignancy worldwide. In the early stages, the development of prostate cancer is dependent on androgens. Over time with androgen deprivation therapy, 20% of prostate cancers progress to a castration-resistant form. Novel treatments for prostate cancers are still urgently needed. Erianin is a plant-derived bibenzyl compound. We report herein that erianin exhibits anti-tumor effects in androgen-sensitive and castration-resistant prostate cancer cells through different mechanisms. Erianin induces endoplasmic reticulum stress-associated apoptosis in androgen-sensitive prostate cancer cells. It also triggers pro-survival autophagic responses, as inhibition of autophagy predisposes to apoptosis. In contrast, erianin fails to induce apoptosis in castration-resistant prostate cancer cells. Instead, it results in cell cycle arrest at the M phase. Mechanistically, C16 ceramide dictates differential responses of androgen-sensitive and castration-resistant prostate cancer cells to erianin. Erianin elevates C16 ceramide level in androgen-sensitive but not castration-resistant prostate cancer cells. Overexpression of ceramide synthase 5 that specifically produces C16 ceramide enables erianin to induce apoptosis in castration-resistant prostate cancer cells. Our study provides both experimental evidence and mechanistic data showing that erianin is a potential treatment option for prostate cancers.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

et al. 2021

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“…Recently, Chen et al studied the effect of erianin on lung cancer and showed that it could inhibit the growth and migration of lung cancer cells via calcium/calmodulin‐dependent ferroptosis, but no apoptotic response was observed in H460 and H1299 lung cancer cells (Chen et al, 2020). However, other studies have shown that erianin can induce apoptosis in many forms of cancer (Chen, Hsieh, et al, 2020; Liu et al, 2019; Mo, Shetti, & Wei, 2019). There are no other reports that indicate whether erianin induces apoptosis and inhibits tumor growth via other mechanisms in lung cancer, and other effects, such as enhancing immunity or antiangiogenic effects in vivo, to the best of our knowledge, have not been assessed.…”

Section: Introductionmentioning

confidence: 96%

Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo

Zhang

Xie

et al. 2021

Phytotherapy Research

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Erianin is a small‐molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg−1 day−1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up‐regulated the levels of interleukin (IL)‐2 and tumor necrosis factor‐α (TNF‐α), decreased IL‐10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.

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“…Erianin, extracted from rare traditional Chinese medicine Dendrobium chrysotoxum Lindl, was a small-molecule natural compound with a wide range of anticancer potential. Erianin has been reported to inhibit colorectal cancer cells growth by downregulating the transcriptional activity of β-catenin (Sun et al, 2020), induce apoptosis in nasopharyngeal carcinoma by decreasing the phosphorylation of ERK1/2 (Liu et al, 2019), and suppress bladder cancer cell growth through JNK pathways and the mitochondrial apoptosis (Zhu et al, 2004). In our previous study, erianin inhibited the growth and migration via inducing Ca/CaM-dependent ferroptosis and inhibiting cell migration in lung cancer cells (Chen et al, 2020a).…”

Section: Introductionmentioning

confidence: 99%

Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation

Chen

Wang

et al. 2021

Front. Pharmacol.

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Erianin, a natural product derived from Dendrobium chrysotoxum Lindl, has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin in bladder cancer cells remain unexplored. In this study, we found that erianin triggered cell death and cell cycle arrest in bladder cancer cells. Then we demonstrated that erianin could promote the accumulation of lethal lipid-based reactive oxygen species (ROS) and the depletion of glutathione (GSH), suggesting the induction of ferroptosis. In the further study, the ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) and GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused cell death, showing ferroptosis played a major role in erianin-caused cell death. In vivo, we also showed that erianin suppressed the tumor growth by inducing ferroptosis. Mechanistically, we demonstrated that nuclear factor E2-related factor 2 (NRF2) inactivation was a key determinant of ferroptosis caused by erianin. In bladder cancer cells, the compound tert-butylhydro-quinone (TBHQ), an activator of NRF2, suppressed erianin-induced ferroptosis. Whereas, NRF2 inhibition used shRNA augmented the ferroptosis response induced by erianin treatment. In conclusion, our data provide the first evidence that erianin can initiate ferroptosis-like cell death and lipid peroxidation in bladder cancer, which will hopefully become a promising anticancer compound for the treatment of bladder cancer.

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Erianin induces cell apoptosis through ERK pathway in human nasopharyngeal carcinoma

Cited by 42 publications

References 24 publications

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

Ceramide Regulates Anti-Tumor Mechanisms of Erianin in Androgen-Sensitive and Castration-Resistant Prostate Cancers

Erianin inhibits human lung cancer cell growth via PI3K/Akt/mTOR pathway in vitro and in vivo

Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation

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